| Autor: |
Philchenkov AA; a R. E. Kavetsky Institute of Experimental Oncology, Pathology and Radiobiology; National Academy of Sciences of Ukraine ; Kyiv , Ukraine., Zavelevich MP; a R. E. Kavetsky Institute of Experimental Oncology, Pathology and Radiobiology; National Academy of Sciences of Ukraine ; Kyiv , Ukraine., Tryndyak VP; b Division of Biochemical Toxicology; National Center for Toxicological Research ; Jefferson , AR USA., Kuiava LM; a R. E. Kavetsky Institute of Experimental Oncology, Pathology and Radiobiology; National Academy of Sciences of Ukraine ; Kyiv , Ukraine., Blokhin DY; c N. N. Blokhin Cancer Research Center ; Moscow , Russian Federation., Miura K; d Miyagi Cancer Center ; Natori , Japan., Silvestri R; e Istituto Pasteur-Fondazione Cenci Bolognetti; Sapienza Università di Roma ; Roma , Italy., Pogribny IP; b Division of Biochemical Toxicology; National Center for Toxicological Research ; Jefferson , AR USA. |
| Jazyk: |
angličtina |
| Zdroj: |
Cancer biology & therapy [Cancer Biol Ther] 2015; Vol. 16 (12), pp. 1820-9. |
| DOI: |
10.1080/15384047.2015.1078026 |
| Abstrakt: |
Recently, a series of novel arylthioindole compounds, potent inhibitors of tubulin polymerization and cancer cell growth, were synthesized. In the present study the effects of 2-(1H-pyrrol-3-yl)-3-((3,4,5-trimethoxyphenyl)thio)-1H-indole (ATI5 compound) on cell proliferation, cell cycle progression, and induction of apoptosis in human T-cell acute leukemia Jurkat cells and their multidrug resistant Jurkat/A4 subline were investigated. Treatment of the Jurkat cells with the ATI5 compound for 48 hrs resulted in a strong G2/M cell cycle arrest and p53-independent apoptotic cell death accompanied by the induction of the active form of caspase-3 and poly(ADP-ribose) polymerase-1 (PARP-1) cleavage. ATI5 treatment also caused non-cell death related mitotic arrest in multidrug resistant Jurkat/A4 cells after 48 hrs of treatment suggesting promising opportunities for the further design of pyrrole-containing ATI compounds as anticancer agents. Cell death resistance of Jurkat/A4 cells to ATI5 compound was associated with alterations in the expression of pro-survival and anti-apoptotic protein-coding and microRNA genes. More importantly, findings showing that ATI5 treatment induced p53-independent apoptosis are of great importance from a therapeutic point of view since p53 mutations are common genetic alterations in human neoplasms. |
| Databáze: |
MEDLINE |
| Externí odkaz: |
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